It is known to perform mass to charge ratio scale calibration of a mass spectrometer by fitting data from known ion peaks by, for example, using a reference standard to the underlying scan law employed by a mass spectrometer. The underlying scan law employed by a mass spectrometer is typically a time of flight function.
It is known to carry out mass to charge ratio calibration before, during or after an acquisition of an unknown analyte.
Internal calibration refers to the addition of a known standard in to an analyte sample itself. However, known internal calibration techniques can be particularly problematic as the standard has to generate similar intensity ions to those of the unknown analyte in order to avoid saturation. Furthermore, the reference ions must have mass to charge ratios which are sufficiently different from the analyte ions in order to avoid interference.
External calibration or lock massing correction of a calibration relies on the stability of the system between the calibration time point and the analyte acquisition time point. However, this approach can be problematic especially if short term perturbations occur to the components within the system due, for example, to effects such as voltage or temperature drift or spikes.
External calibration or lock massing is also problematic and expensive as external calibration or lock massing typically requires a separate dedicated ionisation source. Furthermore, the mass spectrometer has to temporarily switch between the analyte ions and the reference ions which can result in a loss of analyte data.
US 2006/0136158 (Goldberg) discloses a method for recalibrating a mass spectrum of macromolecules or fragments. Information relating to molecules believed to be contained within the sample (such as, for example, information relating to the isotope envelope of molecules believed to be in the sample) is used to tentatively assign specific molecules to peaks in the spectrum. In the case of peptides, fragment peaks on the mass spectrum are difficult to label as belonging to specific sequences of amino acids due to combinations of amino acids having similar masses. Therefore rather than assigning the fragment peaks themselves, mass differences between pairs of fragment ion peaks are determined and tentatively assigned to specific amino acids. Calibration parameters are then adjusted in order to reduce the difference between the measured mass to charge ratio values of the differences between peaks and their “true” values (i.e. the mass values of the corresponding tentatively-assigned molecule).
It is therefore desired to provide an improved method of calibrating or re-calibrating a mass spectrometer.